The intensive use of antibiotics has exerted a selective evolutionary pressure on micro-organisms to produce genetically based resistance mechanisms. Modern medicine and socio-economic behaviour exacerbate the problem of resistance development by creating slow growth situations for pathogenic microbes, e.g. in artificial joints, and by supporting long-term host reservoirs, e.g. in immuno-compromised patients.
In hospital settings, an increasing number of strains of Staphylococcus aureus, Streptococcus pneumoniae, Enterococcus spp., and Pseudomonas aeruginosa, major sources of infections, are becoming multi-drug resistant and therefore difficult if not impossible to treat:                S. aureus is resistant to β-lactams, quinolones and now even to vancomycin;        S. pneumoniae is becoming resistant to penicillin or quinolone antibiotics and even to new macrolides;        Enteroccocci are quinolone and vancomycin resistant and β-lactam antibiotics are inefficacious against these strains;        Enterobacteriacea are cephalosporin and quinolone resistant;        P. aeruginosa are β-lactam and quinolone resistant.        
Further new emerging organisms like Acinetobacter spp. or Clostridium difficile, which have been selected during therapy with the currently used antibiotics, are becoming a real problem in hospital settings. In addition, microorganisms that are causing persistent infections are increasingly being recognized as causative agents or cofactors of severe chronic diseases like peptic ulcers or heart diseases.
Certain heterocyclic compounds as antibacterial agents are known from WO 2007/138974. Compounds for the treatment of multi-drug resistant bacterial infections are disclosed in WO 2006/134378. Piperazine derivatives, containing a quinoline analog moiety, useful in methods of treatment of bacterial infections, are disclosed in WO 02/50040.
Various embodiments of the invention are presented hereafter: